ABSTRACT Background Hemato-oncological diseases have been described as a common cause of secondary immune thrombocytopenia (ITP). So far, studies on patients with active hemato-oncological disease and concurrent ITP are limited, making it difficult to provide clear treatment recommendations. Due to the underlying disease and cancer treatment, this patient population is especially vulnerable. Research design and methods This retrospective, single center pilot study investigated treatment response and time to treatment response in patients with newly diagnosed ITP, comparing those with active hemato-oncological disease, those in remission after malignancy, to those without any underlying malignancy. Results Comparable response rates to ITP treatment were observed across these groups, including the achievement of platelet counts above 30 G/L and complete response (platelet counts ≥ 100 G/L). However, patients with an active hematologic-oncological malignancy exhibited a significantly longer time to platelet recovery after initiating steroid therapy. Conclusion Our preliminary data suggest that standard treatment recommendations for primary ITP may be effective in patients with an active hematologic – oncologic malignancy. However, therapy responses could be significantly delayed, warranting closer monitoring. Given the pilot nature of this study and the limited sample size, these findings should be considered hypothesis-generating and require confirmation in larger studies.

This study aimed to analyze the clinical phenotypes, treatment response, and related risk factors in children with epilepsy to improve diagnosis and prognosis, employing a retrospective-prospective cohort design involving 848 children with non-acquired epilepsy who underwent genetic testing and were followed for 1-5 years to monitor treatment efficacy and development, with participants categorized into Gene-positive (n = 484) and Gene-negative (n = 364) groups for comparative analysis. Results showed that the Gene-negative group had a better treatment response than the Gene-positive group, and multivariate logistic analysis identified specific high-risk factors for poor treatment response in each group: febrile seizures history, delayed language development, concomitant congenital heart disease, and the use of ≥ 4 ASMs in the Gene-positive group, and comorbidities such as autism, intellectual disability, focal seizures, and multiple seizure types in the Gene-negative group. In conclusion, children with positive genetic findings exhibited more significant developmental delays/regression and poorer responses to treatment, underscoring the critical prognostic and therapeutic guidance value of genetic testing, while the treatment response observed at the 3-month mark serves as a significant predictor of long-term prognosis, offering a crucial reference for adjusting therapeutic strategies.

Safety and Effectiveness of Radiation Lobectomy for Primary Liver Cancers Using Resin Microspheres.

Alopecia areata (AA) is an autoimmune, non-scarring hair-loss disorder driven by a T-cell–mediated attack on anagen hair follicles. Beyond visible hair loss, AA is linked to a substantial psychosocial burden, including impaired health-related quality of life and higher rates of anxiety and depression [1]. Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, became the first systemic therapy approved for severe AA [2]. Despite this advance, therapeutic response remains heterogeneous in routine care. Identifying predictors of success is therefore a clinical priority to guide timing, patient selection, and treatment persistence [3]. A tertiary single-center analysis of 72 patients with AA treated with baricitinib between July 2022 and June 2025 was conducted—the cohort's characteristics are described in Table 1. The primary objective was to determine the number of patients who achieved “responder” status, defined as attaining a Severity of Alopecia Tool (SALT) score of 20 or less during follow-up. In addition, a multivariate analysis was performed to identify factors significantly associated with response to baricitinib. For this purpose, a multiple logistic regression was conducted with treatment response (yes/no) as the dependent variable. The independent variables were those that, in descriptive studies, showed a trend toward influencing response outcomes [4, 5]: sex, age at treatment initiation, duration of the current episode, baseline SALT score, treatment duration, presence of nail involvement, and presence of immune-mediated comorbidities. Graphs were generated using GraphPad Prism 8.3.0. Of the 72 patients included in the cohort, 35 (49%) achieved a significant response. Within the cohort, a significant response was observed in 27% at Week 12, 35% at Week 24, 45% at Week 36, 55% at Week 52, 60% at Week 72, 56% at Week 84, 61% at Week 96, and 65% at Week 108 (Figure 1). Our analysis found that patients with a lower baseline SALT score, a shorter duration of the current episode, and a longer treatment duration had statistically significant positive effects on achieving a meaningful clinical response. Patients with a higher baseline SALT score had a significantly lower chance of response [odds ratio (OR) = 0.94 (95% confidence interval (CI): 0.91–0.98), p = 0.003], with each one-point increase in the score decreasing the probability of response by 1.5%. Patients with a longer disease duration also had a lower likelihood of responding [OR = 0.88 (95% CI: 0.78–0.99), p = 0.035], with each additional year of disease reducing the probability of response by 2.7%. Conversely, patients with a longer treatment duration showed a significantly higher chance of response [OR = 1.07 (95% CI: 1.01–1.13), p = 0.038], with each additional month of treatment increasing the probability of response by 1.6%. In the sample, neither sex, nail involvement, nor immune-mediated comorbidities reached statistical significance, although the latter approached the threshold, increasing the likelihood of treatment response by 32.8% [OR = 3.91 (95% CI: 0.95–16.05), p = 0.059]. Our study has certain limitations. It is retrospective and based on real-world data from patients' digital health records, which may involve inconsistencies and a lack of standardization. The sample size is also limited; nonetheless, to our knowledge, this is the largest multivariate analysis to date in a European population on this subject. This study found that baricitinib is a safe and effective treatment for AA and includes the largest multivariate analysis conducted to date, and the first to indicate variations in response probability associated with changes in the independent variables. Shorter disease duration, lower baseline severity, and longer treatment duration were found to be significant predictors of response. Although immune-mediated comorbidities and sex did not reach statistical significance, further research on their possible impact on treatment response is warranted. Therefore, these findings may help optimize patient selection and motivate further research into the complex pathophysiology of AA. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Microaneurysm Reflectivity as a Prognostic Biomarker for Intravitreal Treatment Response in Diabetic Retinopathy.

Explainable artificial intelligence for predicting length of stay and treatment response in pediatric asthma and allergic rhinitis: An irregular fuzzy cellular automata approach across pre- and during-COVID-19 periods.

Pan-cancer analysis identifies FKBP10 as a regulator of tumor immunosuppression and therapeutic response.

Modelling social fear in mice: advancements in social fear conditioning and social defeat paradigms.

Novel therapies like immunotherapy (ICI) and targeted therapy (TT) have significantly improved survival in metastatic melanoma, but treatment failure and/or development of treatment resistance pose major challenges. Radiomics has been shown to be a valuable tool for imaging-based and/or metadata-based (clinomics), non-invasive data analysis to predict therapy response in oncologic patients. This study aims to evaluate the predictive performance of clinical, radiomics, radio-clinomics, and combined radio-clinomics + body composition analysis (BCA) features for treatment response in metastatic melanoma patients undergoing ICI or TT. A retrospective study was conducted on 120 metastatic melanoma patients receiving ICI or TT. Inclusion criteria comprised a minimum of one RECIST 1.1.-identified lesion in pre- and posttherapeutic CT scans as well as metadata including therapy information and clinical features. Radiomics features and BCA biomarkers were extracted. Lesion- and patient-specific models based on clinical, radiomics, radio-clinomics, and BCA parameters were trained twice: with and without therapy information (type and line). All patient-based models showed improved AUCs after inclusion of therapy information. The clinical model achieved modest AUC of 0.657, when compared to imaging included models with AUCs ranging from 0.92 (radiomics) to 0.97 (radio-clinomics + BCA). The lesion-specific radiomics model showed variable performance spanning from poor AUC of 0.76 in peritoneum/soft-tissue lesions to excellent AUC in liver lesions (AUC 0.98). Our results demonstrate that integrating multi-modal data, particularly therapy information and automated BCA features, substantially improves the accuracy of treatment response prediction, highlighting the potential for improved patient stratification and personalized oncologic care.

Cardiovascular MR in Cardiac Amyloidosis: Part II-Clinical Applications in Diagnosis, Prognosis, and Treatment Response.

Prognostic significance of an integrated diagnostic and therapeutic strategy combining bronchoscopy and CT score with monocyte subsets in pediatric patients with severe refractory Mycoplasma pneumoniae pneumonia.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy characterized by progressive muscle weakness. Oxidative stress plays a central role in its pathogenesis. This longitudinal, real-world study evaluated the effect of personalized antioxidant supplementation on quadriceps muscle strength (maximum voluntary contraction; MVCQ), physical activity, and quality of life (QoL) in patients with FSHD1. Patients (aged 15-76) at Montpellier Hospital received tailored antioxidant supplementation (vitamins C and E, zinc, copper, and selenomethionine) based on blood analyses during annual visits: 107 completed one year and 74 continued for two more years of supplementation. Linear mixed model analyses showed a significant annual increase in the MVC of both dominant and non-dominant quadriceps muscles (+0.83kg/year, +1.25kg/year, respectively), improvement in physical activity, especially sports, and in QoL domains, notably physical role. Sex and age influenced outcomes: supplementation benefits were more pronounced in men and younger patients. Supplementation withdrawal resulted in the benefit loss, while attrition was unrelated to disease severity or treatment response. Overall, our findings suggest that personalized antioxidant supplementation may slow FSHD progression, improve muscle strength and quality of life. Baseline muscle strength and clinical scores, including the Brooke upper extremity scale score, allowed stratifying patients in responders and non-responders. These parameters underscore the importance of baseline assessments to predict outcomes and highlight the need of controlled studies to confirm these preliminary results.

Intracranial metastases (IM) are far more common than primary malignant brain tumors, yet remain understudied, representing an important unmet clinical need. Although patients with IM have historically been excluded from clinical trials, thus limiting assessment of intracranial treatment efficacy, their inclusion is increasing; however, patients with suspected leptomeningeal metastatic disease (LMD) remain commonly excluded, likely due to poorer prognosis and anticipated limited treatment response. Despite established treatment response criteria for confirmed LMD, there is limited guidance on how LMD should be diagnosed or excluded in broader IM trials, creating substantial risk for variability and misclassification. This article addresses the gap by proposing MRI-based criteria for classifying IM appearances with respect to LMD suspicion, focusing on the exclusion of LMD, illustrated with real patient examples. IM-related MRI findings are categorized into three groups: (a) imaging consistent with LMD, not requiring cerebrospinal spinal fluid confirmation; (b) equivocal findings warranting further evaluation with cerebrospinal fluid analysis or spinal MRI; and (c) imaging with low suspicion for LMD. Common pitfalls, mimics, and recommended next steps for equivocal findings are discussed. Keywords: Intracranial Metastasis, Leptomeningeal Metastatic Disease, MRI © RSNA, 2026.

Predicting treatment response in psychosis using fMRI: A comprehensive review.

Our previous preclinical studies demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and naproxen significantly inhibited prostate tumorigenesis in a TMPRSS2-ERG fusion-driven model compared to non-fusion models. Since TMPRSS2-ERG fusion-positive tumors display heightened inflammatory signaling and substantial immune infiltration, we hypothesized that the differential efficacy of NSAIDs may arise from their ability to remodel the tumor immune microenvironment. Accordingly, in the present study, we systematically profiled innate and adaptive immune-cell populations: F4/80⁺ macrophages, mast cells, neutrophils, CD3⁺ T cells, CD8⁺ cytotoxic T cells, FoxP3⁺ regulatory T cells, CD20⁺ B cells, IgKC⁺ plasma cells, and Granzyme B⁺ effector cells in highly infiltrated dorso-lateral prostate regions of TMPRSS2-ERG fusion-driven and non-fusion PCa models, with and without NSAID intervention. Our analyses revealed pronounced macrophage infiltration in TMPRSS2-ERG. Ptenflox/flox and Hi-Myc+/ - model, which was further augmented by NSAIDs. Importantly, NSAID intervention shifted macrophage polarization toward an M1-like, pro-inflammatory state, contrasting with the M2-dominant phenotype characteristic of untreated tumors. NSAID treatment reduced mast cell density within the stromal compartment, suggesting suppression of mast cell-mediated tumor-promoting signals. In the fusion model, infiltration of total T cells and CD8⁺ cytotoxic T cells decreased following NSAID exposure, whereas FoxP3⁺ Tregs remained largely unaffected. Both models showed increased B-cell infiltration independent of NSAID efficacy, and no clear correlation was observed between plasma-cell presence and treatment response. Collectively, our findings offer new insight into NSAID-mediated immunomodulation in TMPRSS2-ERG fusion-driven PCa; however, further in-depth immune subtyping and spatial mapping could fully delineate the immunological mechanisms driving NSAID responsiveness.

Although FDA-approved medications for alcohol use disorder are available, their efficacy varies across patients, highlighting the need for novel therapeutics that address inter-individual differences in disease etiology and treatment response. Genetic models, particularly heterogeneous stock (HS) rats, recapitulate human-like genetic diversity and behavioral heterogeneity, enabling the dissection of individual differences in vulnerability to AUD and pharmacotherapeutic sensitivity. P2X4 receptors, which are encoded by the gene P2rx4, are ATP-gated ion channels are inhibited by ethanol and abundantly expressed in neurons found in reward and stress circuits. P2X4 receptors have emerged as key modulators of ethanol sensitivity and consumption in preclinical models. Here, we genetically predicted P2rx4 expression in whole brain in 131 male and female HS rats exposed to chronic intermittent ethanol vapor and phenotyped for self-administration during acute abstinence. Rats were dichotomized into genetically predicted high and low expression groups. We found that higher genetically predicted P2rx4 expression was associated with increased post-vapor intake and escalation. In 32 CIE-escalated rats, ivermectin, a positive allosteric modulator of P2X4 receptors, dose-dependently reduced drinking. We stratified rats into three groups: non-responders, mild responders, and high responders. Electrophysiological recordings from CeA slices revealed that ivermectin differentially enhanced GABAergic IPSCs: high-responders exhibited sustained increases in IPSC frequency and selective amplitude reductions, while the two other groups showed transient frequency increases. All groups displayed prolonged rise times, however non-responders showed extended decay times. These findings suggest that P2rx4 upregulation serves as a vulnerability marker for dependence-like behaviors, with ivermectin attenuating withdrawal-driven alcohol consumption by enhancing CeA GABAergic inhibition.

The YAP1 and EPHA3 receptor tyrosine kinase axis regulates cellular plasticity and treatment response.

Activation of the kynurenine pathway (KP) with resulting accumulation of neuroactive metabolites may be a downstream pathophysiological mechanism of inflammatory depression. The aims of this study were to investigate KP metabolites in inflammatory depression compared to non-inflammatory depression and healthy controls, and whether these metabolites change with nutraceutical interventions with potential KP-modulating effects. We combined data from two antidepressant clinical trials: one with omega-3 polyunsaturated fatty acids (n-3 PUFAs) and one with a Limosilactobacillus reuteri probiotic supplement as the active intervention. Patients with Major Depressive Disorder (MDD) (n=170) were stratified at baseline according to high-sensitivity C-reactive protein (hs-CRP) levels into an inflammatory (hs-CRP ≥1mg/L, n=127) and a non-inflammatory (hs-CRP <1mg/L, n=43) group. We also included 80 non-depressed healthy controls (HC). We investigated between-group differences in KP metabolites at baseline, treatment-associated changes in these biomarkers and how they relate to clinical response. At baseline, the inflammatory depression group had significantly elevated levels of quinolinic acid (QUIN) (p<0.01), 3-hydroxykynurenine (3-HK) (p<0.05), and kynurenine (p<0.05) levels compared to both non-inflammatory depression and HCs. N-3 PUFAs, but not probiotics or placebo, significantly decreased QUIN (p<0.05) and 3-HK (p<0.05). Higher baseline levels and a larger treatment-associated decrease of several KP metabolites were associated with a better clinical response to n-3 PUFAs (p<0.05). In contrast, probiotic supplementation was not associated with significant changes in KP metabolites, and biomarker associations with treatment response were limited in this cohort. We found evidence of KP activation in MDD, but only in an inflammatory subgroup, suggesting that these biological alterations may be specific to a subset of patients with low-grade inflammation. These findings encourage further investigations into whether, and how, biomarkers of KP activation may predict antidepressant response.

Large-scale studies of germline variants in hereditary cancer susceptibility genes among Chinese epithelial ovarian cancer (EOC) patients remain limited. This study assessed the prevalence and clinical significance of germline variants in 21 genes relevant to hereditary breast and ovarian cancer. In this multicenter prospective cohort (February 2017-December 2018), 961 unselected EOC patients underwent germline testing for 21 genes. Variant frequencies were compared with international data, and associations with clinicopathologic characteristics and survival outcomes were evaluated. Pathogenic or likely pathogenic (P/LP) variants were identified in BRCA1 (17.79%), BRCA2 (6.35%), and other homologous recombination (HR)-related genes (2.71%). P/LP variants in non-HR-related genes were rare (0.1%). BRCA1 and BRCA1/2 P/LP variant carriers were more likely to respond to platinum-based chemotherapy (p=.002 and p<.001). Variants of uncertain significance or higher (VUS+) in HR-related genes were associated with better overall survival (hazard ratio, 0.57; p=0.004) and progression-free survival (hazard ratio, 0.75; p=0.02), with a trend more pronounced than that observed for BRCA1/2 VUS+carriers. Over 25% of Chinese EOC patients carry germline HR-related gene variants, which are associated with better treatment response and survival. Broad genetic testing is critical, and the prognostic value of VUS warrants further investigation.

Late-onset rheumatoid arthritis (LORA, onset ≥ 60years, a threshold commonly adopted based on accelerated immunosenescence at this age) represents a growing clinical challenge as population's age, yet therapeutic outcomes in this subgroup remain inadequately characterized. Whether age-related immunological alterations influence treatment response and which molecular pathways underpin potential differences remain unclear. We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Scopus, and Web of Science through 30 September 2025. Studies comparing LORA and young-onset RA (YORA, onset < 60years) patients receiving DMARDs were eligible. Random-effects models estimated pooled effect sizes for disease activity, remission rates, and drug retention. Two-sample Mendelian randomization (MR) assessed causal relationships between genetically proxied plasma IL6 receptor (sIL6R) and TYK2 levels and RA risk using published GWAS summary statistics. Single-cell RNA sequencing data from RA joint tissues (GSE299518; cartilage, meniscus, synovium) were analyzed to map drug target expression and intercellular communication networks. Twelve studies (n>5000 patients) met inclusion criteria. Post-treatment DAS28 scores were higher in LORA than YORA (MD = 0.26, 95% CI = 0.11-0.41, I2 = 0.0%), indicating persistent disease activity. LORA patients achieved clinical remission less frequently with biologic/targeted synthetic DMARDs (RR = 0.36, 95% CI = 0.16-0.79). However, drug retention rates were equivalent between groups (HR = 0.98, 95% CI = 0.87-1.11). MR analysis demonstrated that genetically elevated sIL6R was associated with reduced RA risk (IVW OR = 0.92, 95% CI = 0.87-0.98, p = 0.006), with consistent estimates across sensitivity methods. TYK2 showed a concordant inverse association. Single-cell profiling of 13,979 cells identified inflammatory fibroblasts and macrophages as dominant IL6R/IL6ST/STAT3-expressing populations and principal nodes in IL6 and TNF signaling networks. Pseudotime analysis revealed progressive upregulation of IL6ST and STAT3 along fibroblast differentiation trajectories enriched in synovium. LORA patients exhibit diminished remission rates under current therapeutic regimens despite comparable drug survival. Genetic and single-cell evidence converge on IL6R and TYK2 pathways as mechanistically relevant targets, providing a rationale for age-stratified therapeutic optimization in RA. Key Points • This study evaluates the efficacy and safety of treatments for LORA using meta-analysis, Mendelian randomization, and single-cell RNA sequencing. • LORA patients show different treatment outcomes, particularly in biologic retention rates and clinical remission, compared to YORA patients. • Genetic markers, especially in the IL6R and TYK2 pathways, were identified as key modifiers of drug response in LORA. • The findings highlight the need for personalized treatment strategies for elderly rheumatoid arthritis patients based on genetic and immune system profiles.